Reactions of hydrazonoyl halides 571: Reactions of 1-bromo-2-(5-chlorobenzofuranyl)ethanedione-1-phenylhydrazone

Article abstract of DOI:10.1002/jccs.200800060

Pyrrolo[3,4-c]pyrazole-4,6-diones, pyrazoles, pyrazolo[3,4-d]pyridazines, and pyrazolo[3,4-d]pyrimidines were prepared via 1-bromo-2-(5-chlorobenzofuran- 2-yl)ethanedione-1-phenylhydrazone with N-arylmalemides and active methylene. All newly synthesized c

Full text of DOI:10.1002/jccs.200800060

406
Journal of the Chinese Chemical Society, 2008, 55, 406-413
Reactions of Hydrazonoyl Halides 571: Reactions of
1-Bromo-2-(5-chlorobenzofuranyl)ethanedione-1-phenylhydrazone
Abdou O. Abdelhamid,a* Ahmed H. El-Ghandourb and Ahmed A. M. El-Reedyb
aDepartment of Chemistry, Faculty of Science, Cairo University, Giza 12613, A. R. Egypt
bDepartment of Chemistry, Faculty of Science, Ben-Suef University, Ben-Suef, A. R. Egypt
Pyrrolo[3,4-c]pyrazole-4,6-diones, pyrazoles, pyrazolo[3,4-d]pyridazines, and pyrazolo[3,4-d]pyr-
imidines were prepared via 1-bromo-2-(5-chlorobenzofuran-2-yl)ethanedione-1-phenylhydrazone with
N-arylmalemides and active methylene. All newly synthesized compounds were confirmed by elemental
analysis and spectral data.
Keywords: Pyrrolo[3,4-c]pyrazoles; Pyrazolo[3,4-d]pyridazines; Pyrazolo[3,4-d]pyrimidines;
Pyrazoles; Nitrilimine.
INTRODUCTION
As part of our continued interest in biologically ac-
Compounds 3a-d were oxidized by p-chloranil in
boiling xylene to give 1-aryl-3-(5-chlorobenzofuran-2-car-
bonyl)-5-phenyl-1H-pyrrolo[3,4-c]pyrazole-4,6-diones
4a-d, respectively (Scheme I). Structure of 4 was eluci-
dated by elemental analysis and spectral data. Thus, IR
spectrum of 4b revealed bands at 1789, 1718, 1668 (CO’s)
and 1621 (C=N).
tive heterocycles, we note pyrazoles and annelated pyra-
zoles have long been known to exhibit diverse biological
activities. Among these activities include their use as anti-
pyretic,2 analgesic drugs,3,4 antitumor,5 hypnotic,6 fungi-
cides7 and herbicidal8 agents. Moreover, benzofurans are
very important compounds due to their broad spectrum of
biological and pharmacological effects. Benzofurans are
considered non-steroidal anti-inflammatory drugs (NSAID),
where the action of (NSAID) is lowering the prostaglandin
production through inhibition of cyclooxygenase (COX).
Benzofurans are among the COX-2 inhibitors.9,10 In addi-
tion, diverse pharmacological properties have been associ-
ated with benzofuran derivatives.11-15 We report here sev-
eral heterocyclic compounds expected to possess biologi-
cal activity containing benzofuran moiety.
Scheme I
RESULTS AND DISCUSSION
Treatment of 1-bromo-2-(5-chlorobenzofuran-2-yl)-
ethanedione-1-phenylhydrazone (1)1 with the appropriate
N-arylmaleimides 2a-d16 in boiling toluene containing
triethylamine yielded 1-aryl-3-(5-chlorobenzofuran-2-car-
bonyl)-5-phenyl-3a,6a-dihydro-1H-pyrrolo[3,4-c]pyra-
zole-4,6-diones 3a-d, respectively (Scheme I). Structure 3
was inferred from spectral data, elemental analysis and oxi-
dation. Thus IR spectra of 3a-d revealed bands near 1790-
1720 cm-1 and 1710-1690 cm-1 (-CONArCO-)17 and 1640
(CO, conjugated).
Also, 1 reacted with each of 2,4-pentandione, benzo-
ylacetonitrile, malononitrile and benzenesulfonylaceto-
phenone in ethanolic sodium ethoxide solution to yield
4-acetyl-3-[(5-chlorobenzo[d]furan-2-yl)carbonyl]-5-
methylpyrazole (5), 3-[(5-chlorobenzo[d]furan-2-yl)car-
bonyl]-1,5-diphenylpyrazole-4-carbonitrile (6), 5-amino-
3-[(5-chlorobenzo[d]furan-2-yl)carbonyl]-1-phenylpyra-
zole-4-carbonitrile (7) and 3-(5-chlorobenzo[d]-1,5-di-
phenyl-4-(phenylsulfonyl)benzenepyrazole (8), respec-
* Corresponding author. E-mail: Abdou_abdelhamid@yahoo.com

Reactions of Hydrazonoyl Halides 57
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 407
Scheme II
tively (Scheme II). Structure 5 was established by elemen-
tal analysis, spectral data and chemical transformation.
Thus, 5 reacted with hydrazine hydrate in boiling ethanol to
afford 7-(5-chlorobenzofuran-2-yl)-3,4-dimethyl-2-phen-
yl-2H-pyrazolo[3,4-d]pyridazine (9). Thus, IR spectrum of
9 revealed no bands between “1650-2000” attributed to the
absence of a CO group.18
has the loss of the element of water. Alternatively, dehy-
drobromination of 1 by the carbanion may occur to give
nitrilium imide intermediate 10. Addition of the latter to the
enol double bond followed by dehydration would lead to
the product (sequence B). Although no attempt was made
to isolate or identify the reaction intermediate, the substitu-
tion sequence seems to be much more plausible for the re-
action studied than sequence B. This is because, if nitrilium
imide (10) was involved, it might dimerize to yield tetra-
zine 12. The lack of formation of the latter in these reac-
tions seems to favour sequence A.
The foregoing results may be considered in terms of
two alternative mechanisms presented in Scheme III. In the
substitution Sequence (A), it is assumed that the carbanion
attacks the hydrazonoyl bromide 1 to give the open chain
intermediate hydrazone 11, which then through cyclization
Compound 7 reacted with each of formic acid and
formamide to give 3-[(5-chlorobenzo[d]furan-2-yl)car-
bonyl]-1-phenyl-5-hydro-pyrazolo[3,4-d]pyrimidin-4-one
13 and 4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-3-yl-
5-chlorobenzo[d]furan-2-yl ketone 14, respectively (Scheme
IV).
Scheme III
Scheme IV
Treatment of 1 with each of 1-cyanocinnamonitrile
and benzalacetophenone in boiling toluene containing tri-
ethylamine to give a product seemed to be 3-[(5-chloro-
benzo[d]furan-2-yl)carbonyl]-1,4-di-phenyl-pyrazole-5-
carbonitrile 15 or its isomers 6 and 1,5-diphenyl-4-(phen-
ylcarbonoyl)(2-pyrazolin-3-yl)chlorobenzo[d]furan-2-yl

408 J. Chin. Chem. Soc., Vol. 55, No. 2, 2008
Abdelhamid et al.
Scheme V
ketone 16 or 17, respectively (Scheme V). Structures 15
and 16 were established by elemental analysis, spectral
data and chemical transformation. Thus, pyrazoline 16 was
oxidized to pyrazole 18 by boiling with p-chloranil in xy-
lene. Also, treatment of 1 with dibenzoylmethane in eth-
anolic sodium ethoxide solution to give 1,5-diphenyl-4-
(phenylcarbonyl)pyrazol-3-yl-5-chlorobenzo[d]furan-2-yl
ketone 18, which have in all aspects (m.p., mixed m.p. and
spectra) with sample obtained from oxidation 16.
furan-2-yl)-2-phenyl-6-hydropyrazolo[3,4-d]pyridazin-7-
one (24a).
Analogously, compound 21 reacted with the appro-
priate hydrazonoyl halides 21(b-e) in boiling toluene in the
presence of triethylamine to give pyrazoles 23(b-e), re-
Scheme VI
On the other hand, 5-chloro-2-acetylbenzofuran re-
acted with dimethylformamide-dimethylacetal in boiling
xylene to afford 3-(dimethylamino)-1-(5-chlorobenzo[d]-
furan-2-yl)prop-2-en-1-one (20) in a good yield (Scheme
VI). Structure 20 was confirmed by elemental analysis,
spectral data and chemical transformation. Thus, com-
pound 20 reacted with C-ethoxycarbonoyl-N-phenylhy-
drazonoyl chloride 21a in boiling toluene, containing tri-
ethylamine to afford ethyl 2-{4-[(5-chlorobenzo[d]furan-
2-yl)carbonoyl]-1-phenylpyrazol-3-yl}-2-oxoacetate 23a
or its isomer 22a. Structure of the product was confirmed
by elemental analysis, spectral data and chemical transfor-
mation. The product reacted with hydrazine hydrate in
boiling ethanol under reflux to give 4-(5-chlorobenzo[d]-

Reactions of Hydrazonoyl Halides 57
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 409
spectively (Scheme VI). Pyrazoles 23b-e reacted with boil-
ing hydrazine hydrate in ethanol under reflux to afford
pyrazolo[3,4-d]pyridazines 24a-d, respectively.
EXPERIMENTAL
All melting points were determined on an electro-
thermal apparatus and are uncorrected. IR spectra were re-
corded (KBr discs) on a Shimadzu FT-IR 8201 PC spectro-
photometer. 1H NMR spectra were recorded in CDCl3 and
(CD3)2SO solutions on a Varian Gemini 300 MHz spec-
trometer and chemical shifts are expressed in d units using
TMS as an internal reference. Mass spectra were recorded
on a GC-MS QP1000 EX Shimadzu. Elemental analyses
were carried out at the Microanalytical Center of Cairo
University.
ANTIMICROBIAL ACTIVITY
The tested organisms were gram +ve bacteria [Staph-
ylococcus aureus (Atcc 25923), Streptococcus pyogenes
(Atcc 19615)] and gram -ve bacteria, Pseudomonas syrin-
gae pv. Phaseolicola (GspB 2828) and Pseudomonas fluo-
rescens (S 97).
The study followed a modification of the filter-pa-
per-disc (3 discs/compound) method19 used in determining
the reaction of antibiotics against various bacteria and
fungi. Unless otherwise noted, the medium in which the or-
ganisms were seeded was potato-dextrose agar (PDA)
which contains an infusion of 200 g potatoes, 6 g dextrose
and 15 g agar.
1-Aryl-3-(5-chlorobenzofuran-2-carbonyl)-5-phenyl-
3a,6a-dihydro-1H-pyrrolo[3,4-c]pyrazole-4,6-diones
3a-d
An equimolar amount of 1, the appropriate of N-aryl-
malemide 2a-e and triethyl amine (5 mmoles) in dry tolu-
ene (25 mL) were boiled under reflux for 3 hrs. The reac-
tion mixture was evaporated under reduced pressure and
then triturated with petroleum ether (40-60 °C). The result-
ing solid was collected and recrystallized from the proper
solvent to give 3a-d, respectively (Tables 2 and 3).
1-Aryl-3-(5-chlorobenzofuran-2-carbonyl)-5-phenyl-
1H-pyrrolo[3,4-c]pyrazole-4,6-diones 4a-d
The tested compounds were dissolved in the N,N-
dimethylformamide, which had no inhibition activity, to
get a solution of 100 mg/mL and 200 g/mL concentration.
The antibiotic cephalexin with a concentration of 80
mg/mL, was used as a control for inhibition zones. After in-
cubation for 48 h at 27 °C with the bacteria and for 96 h at
24 °C with the fungi, inhibition of the organisms shown by
a clear zone surrounding each paper disc was measured.
Equimolar amounts of the appropriate 3a-e and p-
chloranil (5 mmoles) in xylene (25 mL) were heated for 48
Table 1. Response of various microorganisms to some synthesized compounds in vitro (culture)
Mean* of inhibition zone (mm) toward organisms
Gram-positive bacteria
S. a. S. p.
Gram-negative bacteria
Fungi**
Aspergillus
niger
Compound
No.
P. s. pv.
P. fluorescens Fusariam o.
Phaseolicol
H.
L.
H.
L.
H.
L.
H.
L.
H.
L.
H.
L.
4a
34.1 26.2 29.3 18.0
31.6 19.3 33.4 20.3
-
X
0.0
X
X
X
X
X
X
X
X
X
X
-
X
0.0
X
X
X
X
X
X
X
X
X
X
X
X
-
X
X
-
-
4c
3.3
-
2.0
-
-
5
-
X
-
¾
¾
¾
¾
¾
¾
¾
¾
42.7
X
X
X
X
X
X
X
X
X
X
-
X
X
X
X
X
X
X
X
X
-
X
6
04.9 00.0
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
¾
8
¾
¾
X
X
X
X
X
X
X
X
23c
23b
23d
23e
24c
54e
Control
¾
¾
¾
¾
X
X
¾
40.4
* = Calculated from 3 values.
** = Identified depending on morphological and microscopic character.
X = not performed.
- = No effect.

410 J. Chin. Chem. Soc., Vol. 55, No. 2, 2008
Abdelhamid et al.
Table 2. Characterization data of the newly synthesized compounds
Calcd. /Found%
Comp.
No.
Mp. °C
Solvent
Color
Yield%
Mol. Formula
(Mol. Wt.)
C
H
N
S
162-65
Dioxane
152-55
AcOH
203-205
AcOH
249-52
AcOH
239-42
AcOH
205-208
AcOH
199-202
AcOH
> 300
DMF
162-65
EtOH
197-200
EtOH
> 300
AcOH
225-28
AcOH
> 300
DMF
> 300
DMF
285-8
AcOH
183-85
EtOH
218-20
AcOH
228-30
AcOH
243-46
AcOH
143-45
EtOH
92-95
EtOH
237-40
EtOH
187-90
AcOH
117-20
EtOH
244-46
AcOH
> 300
Yellow
68
Yellow
70
Yellow
65
Yellow
61
Yellow
63
Yellow
66
Yellow
58
Yellow
60
Brown
70
Brown
67
Yellow
66
Colorless
74
Yellow
60
Colorless
62
Yellow
59
Brown
70
Orange
72
Yellow
60
Yellow
55
Yellow
75
Colorless
65
Yellow
64
Yellow
60
Yellow
64
Colorless
71
Yellow
60
Yellow
62
Yellow
71
C26H16ClN3O4
469.89
C27H18ClN3O4
483.92
C27H18ClN3O5
499.91
C26H15Cl2N3O4
504.33
C26H14ClN3O4
467.87
C27H16ClN3O4
481.90
C27H16ClN3O5
497.90
C26H13Cl2N3O4
502.32
C21H15ClN2O3
378.80
C25H14ClN3O2
423.86
C19H11ClN4O2
362.78
C30H19ClN2O4S
539.01
C21H15ClN4O
374.83
C20H11ClN4O3
390.79
C20H12ClN5O2
389.80
C25H14ClN3O2
423.86
C31H21ClN2O3
504.98
C31H19ClN2O3
502.96
C31H19ClN4O
498.98
C13H12ClNO2
249.70
C21H15ClN2O4
394.82
C25H16ClN3O3
441.88
C20H13ClN2O3
364.79
C25H15ClN2O3
426.86
66.46
66.61
67.02
67.20
64.87
65.01
61.92
61.78
66.75
66.89
67.30
67.48
65.13
65.31
62.17
62.32
66.58
66.38
70.84
70.64
62.91
63.09
66.85
67.01
67.29
67.48
61.47
61.67
61.63
61.82
70.84
70.65
73.73
73.91
74.03
74.17
74.62
74.81
62.53
62.71
63.89
64.03
67.95
68.09
65.85
65.66
70.34
70.49
64.69
64.88
62.91
63.12
66.58
66.78
71.01
71.18
65.21
65.04
3.43
3.23
3.75
3.95
3.63
3.81
3.00
3.19
3.02
3.18
3.35
3.59
3.24
3.09
2.61
2.81
3.99
4.11
3.33
3.50
3.06
2.90
3.55
3.69
4.03
3.88
2.84
3.01
3.10
3.25
3.33
3.50
4.19
4.39
3.81
3.99
3.84
3.98
4.84
4.96
3.83
4.02
3.65
3.44
3.59
3.78
3.54
3.35
2.81
2.62
3.06
3.19
3.63
3.48
3.58
3.76
2.84
3.04
08.94
09.10
08.68
08.49
08.41
08.28
08.33
08.52
08.98
09.19
08.72
08.58
08.44
08.31
08.37
08.19
07.40
07.59
09.91
10.06
15.44
15.63
05.20
05.36
14.95
15.09
14.34
14.52
17.97
17.77
09.91
10.09
05.55
05.39
05.57
05.38
11.23
11.41
05.61
05.81
07.10
07.31
09.51
09.71
07.68
07.48
06.56
06.74
05.59
05.75
15.44
15.62
15.53
15.69
13.25
13.09
11.27
11.45
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
5.95
6.09
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
--
3a
3b
3c
3d
4a
4b
4c
4d
5
6
7
8
9
13
14
15
16
18
19
20
23a
23b
23c
23d
23e
24a
24b
24c
24d
C27H14Cl2N2O4
501.33
C19 H11ClN4O2
362.78
AcOH
267-70
AcOH
256-59
AcOH
> 300
C20H13ClN4O
360.81
C25H15ClN4O
422.88
C27H14Cl2N4O2
497.34
Yellow
73
DMF

Reactions of Hydrazonoyl Halides 57
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 411
Table 3. Spectral data of some newly synthesized compounds
Compound
No.
Spectral data
3a
3b
1H NMR: d = 5.33 (d, J = 8 Hz, 1H), 5.56 (d, J = 8 Hz, 1H), 7.14-7.36 (m, 5H), 7.38-7.43 (m,
5H), 7.44-7.36 (m, 3H) and 7.95 (s, 1H).
13C NMR: d = 32.12, 50.42, 111.65, 113.21, 116.73, 117.39, 121.20, 121.63, 123.35, 124.44,
124.72, 129.18, 130.25, 132.36, 135.44, 143.52, 155.21, 162.36, 171.45, 175.11, 178.48.
1H NMR: d = 2.35 (s, 3H), 5.31 (d, J = 8 Hz, 1H), 5.40 (d, J = 8 Hz, 1H), 7.13-7.26 (m, 5H),
7.40-7.58 (m, 4H), 7.70-7.74 (m, 3H) and 7.97 (s, 1H).
13C NMR: d = 24.35, 111.65, 113.21, 116.73, 117.41, 121.15, 121.63, 123.33, 124.74, 129.24,
130.25, 132.36, 135.44, 143.52, 155.21, 162.36, 171.45, 175.11, 178.46.
1H NMR: d = 3.78 (s, 3H), 5.40 (d, J = 8 Hz, 1H), 5.62 (d, J = 8 Hz, 1H), 7.13-7.26 (m, 5H),
7.40-7.58 (m, 4H), 7.70-7.74 (m, 3H) and 7.91 (s, 1H).
3c
3d
4a
1H NMR: d = 5.30 (d, J = 8 Hz, 1H), 5.53 (d, J = 8 Hz, 1H), 7.13-7.26 (m, 5H), 7.40-7.58 (m,
4H), 7.70-7.74 (m, 3H) and 7.97 (s, 1H).
1H NMR: d = 7.16-7.42 (m, 8H), 7.45-7.61 (m, 3H) and 7.91 (s, 1H).
13C NMR: d = 107.42, 111.63, 113.21, 116.73, 117.42, 121.24, 121.63, 123.32, 124.44, 124.72,
126.35, 129.21, 130.22, 132.31, 135.15, 143.44, 155.21, 162.36, 171.45, 175.11, 178.34.
1H NMR: d = 2.32 (s, 3H), 7.16-7.42 (m, 9H), 7.45-7.61 (m, 3H) and 7.91 (s, 1H).
MS: m/z = 504 (1.6%), 502 (4.2%), 475 (4.5%), 475 (13.5%), 351 (39%), 349 (100%), 322
(3.8%), 181 (10.2%), 179 (33.6%), 123 (17.3%), 125 (6.8%), 104 (7%) and 77 (16.2%).
1H NMR: d = 3.68 (s, 3H), 7.16-7.42 (m, 9H), 7.45-7.61 (m, 3H) and 7.91 (s, 1H).
1H NMR: d = 7.16-7.42 (m, 8H), 7.45-7.61 (m, 3H) and 7.91 (s, 1H).
1H NMR: d = 2.52 (s, 3H), 2.59 (s, 3H), 7.26-7.59 (m, 8H) and 8.10 (s, 1H).
13C NMR: d = 9.21, 29.04, 113.12, 116.73, 120.32, 121.42, 124.35, 124.77, 126.33, 128.75,
129.43, 139.72, 140.24, 155.35, 159.35, 175.22, 199.85.
4b
4c
4d
5
6
1H NMR: d = 7.21-7.63 (m, 13H) and 8.20 (s, 1H).
13C NMR: d = 106.21, 113.35, 116.73, 120.23, 124.14, 124.72, 126.31, 127.52, 128.75, 129.41,
132.12, 133.21, 139.74, 142.23, 143.35, 155.15, 159.05, 170.14.
7
1H NMR: d = 7.09 (s, br., 2H), 7.55-7.81 (m, 7H), 8.02 (d, 1H) and 8.25 (s, 1H)
13C NMR: d = 94.12, 113.35, 116.73, 120.12, 124.44, 124.72, 126.25, 128.73, 129.44, 132.72,
139.71, 140.24, 151.25, 155.05, 160.08.
9
1H NMR: d = 2.80 (s, 3H), 2.97 (s, 3H), 7.26-7.34 (m, 1H), 7.57-7.63 (m, 7H) and 8.10 (s, 1H).
13C NMR: d = 8.72, 22.74, 102.12, 107.35, 113.24, 121.21, 124.31, 125.35, 128.71, 129.43,
137.00, 139.72, 148.35, 150.17, 153.16, 156.12, 158.22.
13
14
15
1H NMR: d = 7.26-7.34 (m, 5H), 7.57-7.63 (m, 4H), 7.79 (s, 1H) and 8.85 (s, 1H).
13C NMR: d = 107.12, 113.36, 116.15, 120.21, 124.44, 126.24, 128.71, 129.42, 132.34, 139.72,
141.12, 142.21, 145.35, 155.12, 159.11, 161.12, 175.11.
1H NMR: d = 6.24 (s, 2H), 7.26-7.34 (m, 5H), 7.57-7.63 (m, 4H) and 7.79 (s, 1H).
13C NMR: d = 101.12, 113.31, 116.23, 120.41, 121.14, 124.44, 126.10, 128.71, 129.42, 132.83,
139.75, 148.14, 151.25, 155.34, 156.32, 158.31, 160.14.
1H NMR: d = 4.74 (d, J = 8 Hz), 1H), 5.36 (d, d, J = 8 Hz, 1H) and 7.07-7.98 (m, 18H) and
8.14 (s, 1H).
13C NMR: d = 113.14, 114.23, 116.34, 120.21, 124.25, 126.20, 127.34, 129.44, 132.21, 137.72,
148.15, 155.13, 159.25, 175.41.
20
1H NMR: d = 2.97 (s, 3H), 3.17 (s, 3H), 5.78-5.84 (d, 1H), 7.29-7.61 (m, 4H) and 7.85-7.91 (d,
1H).
13C NMR: d = 43.10, 92.23, 113.31, 116.14, 120.44, 124.21, 128.32, 135.24, 155.22, 160.11,
178.21.
23a
1H NMR: d = 1.16 (t, J = 7 Hz, 3H), 4.21 (q, J = 7 Hz, 2H), 7.25-7.80 (m, 9H) and 8.48 (s, 1H).
13C NMR: d = 14.12, 60.92, 110.11, 116.31, 120.21, 121.44, 124.12, 128.13, 129.43, 131.08,
139.12, 144.14, 155.12, 160.18, 161.25, 167.34.
23c
23d
1H NMR: d = 2.69 (s, 3H), 7.25-7.80 (m, 9H) and 8.42 (s, 1H).
1H NMR: d = 7.15-7.45 (m, 10H), 7.80-7.83 (d, 2H), 8.09-8.11 (d, J = 6 Hz, 2H) and 8.71 (s,
1H).

412 J. Chin. Chem. Soc., Vol. 55, No. 2, 2008
Abdelhamid et al.
hrs. The reaction mixture was cooled, washed with sodium
hydroxide (0.1 N) and then with water. The reaction mix-
ture was evaporated and triturated with petroleum ether
(40-60 °C). The resulting solid was collected and recrys-
tallized from acetic acid to give 4a-e (Tables 2 and 3).
3-[(5-Chlorobenzo[d]furan-2-yl)carbonyl]-1,4-disubsti-
tuted pyrazoles 6-8
for 3 hrs. The hot solution was filtered off and the filtrate
was evaporated and triturated with petroleum ether (40-60
°C). The resulting solid was collected and recrystallized
from acetic acid to give 16 (Tables 2 and 3).
3-[(5-Chlorobenzo[d]furan-2-yl)carbonyl]-1,5-diphen-
ylpyrazole-4-ylphenyl ketone (18)
Method A: Dibenzoylmethane (1.12 g, 5 mmoles)
was added to a solution of sodium ethoxide (0.12 g-atom, 5
mmoles in ethanol (15 mL)) while stirring, then 1 (1.80 g, 5
mmoles), stirring for 3 hrs at room temperature. The resul-
tant solid was collected and recrystallized from ethanol to
give 18 (Tables 2 and 3).
General Method
The appropriate 2,4-pentanedione, benzoylacetoni-
trile, malononitrile, or w-benzenesulfinylaceophenone (5
mmoles) was added to a solution of sodium ethoxide [0.12
g-atom, 5 mmol in ethanol (15 mL)] while stirring, then 1
(1.80 g, 5 mmoles) was added while stirring at room tem-
perature. The reaction mixture was stirred for 3 hrs and the
resulting solid was collected and recrystallized from etha-
nol to give 6-8, respectively (Tables 2 and 3).
Method B: Equimolar amounts of the pyrazoline 16
and p-chloranil (5 mmoles) in xylene (25 mL) were heated
for 48 hrs. The reaction mixture was cooled, washed with
sodium hydroxide (0.1 N) and then with water. The reac-
tion mixture was evaporated and triturated with petroleum
ether (40-60 °C). The resultant solid was collected and
recrystallized from acetic acid to give 18 (Tables 2 and 3).
3-(Dimethylamino)-1-(5-chlorobenzo[d]furan-2-yl)prop-
2-en-1-one (20)
3-[(5-Chlorobenzo[d]furan-2-yl)carbonyl]-1,4-diphen-
ylpyrazole-5-carbonitrile (15)
A mixture of each 1, 1-cyanocinamonitrile and tri-
ethylamine (5 mmoles) in dry toluene (20 mL) was heated
for 3 hrs. The hot solution was filtered off; the filtrate was
evaporated under reduced pressure and triturated with pe-
troleum ether (40-60 °C). The resulting solid was collected
and recrystallized from acetic acid to give pyrazole 15
(Tables 2 and 3).
Equimolar amounts of 2-acetyl-5-chlrobenzo[d]fu-
ran (1) and dimethlformamide-dimethylacetal (5 mmoles)
were boiled in dry xylene (40 mL) for 4 hrs. The hot solu-
tion was evaporated to half its volume and then cooled. The
resultant solid was collected and recrystallized to give 20
(Tables 2 and 3).
3-[(5-Chlorobenzo[d]furan-2-yl)carbonyl-1-phenyl-5-
hydropyrazolo[3,4-d]pyrimidin-4-one (13)
A mixture of aminocyanopyrazole 7 (1.80 g, 5
mmoles) and formic acid (5 mL) in N,N-dimethylform-
amide (10 mL) was heated for 5 hrs. The reaction mixture
was poured onto crushed ice (20 g). The resulting solid was
collected and recrystallized from acetic acid to give 7
(Tables 2 and 3). IR (cm-1): 3350 (NH), 1686, 1655 (CO’s).
4-Amino-1-phenylpyrazolo[3,4-d]pyrimidine-3-yl-5-
chlorobenzo[d]furan-2-yl ketone (14)
3-[(5-Chlorobenzo[d]furan-2-yl)carbonyl]-1-pphenyl-
pyrazol-4-yl-4-substituted ketone (23a-e)
Equimolar amounts of each of the appropriate 1,
21a-d and 20 (5 mmoles) were boiled in dry toluene (20
mL) containing triethylamine (0.5 g (1.5 mL), 5 mmoles)
for 3 hrs. The hot solution was filtered off and the filtrate
was evaporated under reduced pressure and triturated with
petroleum ether (40-60 °C). The resultant solid was col-
lected and recrystallized to give 23a-e, respectively (Tables
2 and 3).
A mixture of aminocyanopyrazole 7 (1.8 g, 5
mmoles) and formamide (5 mL) in N,N-dimethylform-
amide (10 mL) was boiled for 5 hrs. The reaction mixture
was poured onto crushed ice (20 g). The resulting solid was
collected and recrystallized from acetic acid to give 14
(Tables 2 and 3). IR (cm-1): 3290, 3185 (NH2), 1655
(CO’s).
Pyrazolo[3,4-d]pyridazines (9, 19 and 24a-d)
Equimolar amounts of each of the appropriate pyra-
zoles, 6, 18, or 23a-e (5 mmoles) and hydrazine hydrate (1
mL, 99%) in ethanol (20 mL) were boiled for 2 hrs. The re-
sultant solid was collected and recrystallized to give pyr-
azolo[3,4-d]pyridazines 9, 19 and 24a-d, respectively
(Tables 2 and 3).
3-[(Chlorobenzo[d]furan-2-yl)carbonyl]-1,5-diphen-
yl(2-pyrazolin-4-yl)phenyl ketone (16)
Equimolar amounts of each of 1 and 1,3-diphenyl-
prop-2-ene-1-one (1.02 g, 5 mmoles) were heated in dry to-
luene containing triethylamine (0.5 g (1.5 mL), 5 mmoles)
Received June 12, 2007.

Reactions of Hydrazonoyl Halides 57
J. Chin. Chem. Soc., Vol. 55, No. 2, 2008 413
Walters, M. H.; Smith, J. H.; Nichols, J. P.; Simons, C.
Bioorg. Med. Chem. Lett. 1999, 9, 2105.
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